Biomolecular condensates can function as inherent catalysts.
Xiao Guo, Mina Farag, Naixin Qian, Xia Yu, Anton Ni, Yuefeng Ma, Wen Yu, Matthew R King, Vicky Liu, Joonho Lee, Richard N Zare, Wei Min, Rohit V Pappu, Yifan Dai
Author Information
Xiao Guo: Department of Biomedical Engineering, Center for Biomolecular Condensates, Washington University in St. Louis, St. Louis, MO 63130.
Mina Farag: Department of Biomedical Engineering, Center for Biomolecular Condensates, Washington University in St. Louis, St. Louis, MO 63130.
Naixin Qian: Department of Chemistry, Columbia University, New York, NY 10027.
Xia Yu: Department of Chemistry, Stanford University, Stanford, CA 94305.
Anton Ni: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138.
Yuefeng Ma: Department of Biomedical Engineering, Center for Biomolecular Condensates, Washington University in St. Louis, St. Louis, MO 63130.
Wen Yu: Department of Biomedical Engineering, Center for Biomolecular Condensates, Washington University in St. Louis, St. Louis, MO 63130.
Matthew R King: Department of Biomedical Engineering, Center for Biomolecular Condensates, Washington University in St. Louis, St. Louis, MO 63130.
Vicky Liu: Department of Biomedical Engineering, Center for Biomolecular Condensates, Washington University in St. Louis, St. Louis, MO 63130.
Joonho Lee: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138.
Richard N Zare: Department of Chemistry, Stanford University, Stanford, CA 94305.
Wei Min: Department of Chemistry, Columbia University, New York, NY 10027.
Rohit V Pappu: Department of Biomedical Engineering, Center for Biomolecular Condensates, Washington University in St. Louis, St. Louis, MO 63130.
Yifan Dai: Department of Biomedical Engineering, Center for Biomolecular Condensates, Washington University in St. Louis, St. Louis, MO 63130.
We report the discovery that chemical reactions such as ATP hydrolysis can be catalyzed by condensates formed by intrinsically disordered proteins (IDPs), which themselves lack any intrinsic ability to function as enzymes. This inherent catalytic feature of condensates derives from the electrochemical environments and the electric fields at interfaces that are direct consequences of phase separation. The condensates we studied were capable of catalyzing diverse hydrolysis reactions, including hydrolysis and radical-dependent breakdown of ATP whereby ATP fully decomposes to adenine and multiple carbohydrates. This distinguishes condensates from naturally occurring ATPases, which can only catalyze the dephosphorylation of ATP. Interphase and interfacial properties of condensates can be tuned via sequence design, thus enabling control over catalysis through sequence-dependent electrochemical features of condensates. Incorporation of hydrolase-like synthetic condensates into live cells enables activation of transcriptional circuits that depend on products of hydrolysis reactions. Inherent catalytic functions of condensates, which are emergent consequences of phase separation, are likely to affect metabolic regulation in cells.
